Nivolumab (Opdivo), an antibody that blocks the PD-1 receptor and restores T-cell anti-tumor activity, appeared safe and was associated with disease control and stabilization in a Phase 1/2 study of patients with hepatocellular carcinoma, according to late-breaking results from the CheckMate 040 study presented at the AASLD Liver Meeting last month in Boston.

Hepatocellular carcinoma (HCC), a type of primary liver cancer, can develop over years or decades in people with chronic hepatitis B or C virus (HBV or HCV) infection, heavy alcohol use, or other causes of liver damage. People with hepatitis C who have progressed to liver cirrhosis remain at risk for HCC even after being cured with effective antiviral therapy.

HCC is often diagnosed late when it is difficult to treat, and it is a leading cause of cancer death worldwide. Sorafenib (Nexavar), a multikinase inhibitor, is the standard of care for HCC that cannot be surgically removed or resected, but it typically extends survival by only a few months, and more effective therapies are urgently needed.

Bruno Sangro from Clinica Universidad de Navarra in Pamplona, Spain, presented findings from Bristol-Myers Squibb's CheckMate 040 trial, evaluating different doses of nivolumab in people with advanced HCC, including those with chronic HBV or HCV infection.

Nivolumab is currently FDA-approved for treatment of advanced melanoma, non-small cell lung cancer, renal cell carcinoma, head and neck cancers, and Hodgkin lymphoma.

CheckMate 040 (study CA209-040/NCT01658878) included a Phase 1 dose escalation segment that enrolled 48 participants and a Phase 2 dose expansion segment that enrolled 214 people. Patients in the first part received ascending doses of 0.1, 0.3, 1.0, 3.0, and 10.0 mg/kg nivolumab given by intravenous infusion every 2 weeks. In the second part everyone received the selected 3.0 mg/kg dose. There were no placebo or comparator drug arms in this early trial.

Participants had biopsy-confirmed advanced HCC not amenable to curative surgical resection. They had Child-Pugh scores <7 (escalation) or <6 (expansion), and AST and ALT liver enzyme levels <5 times the upper limit of normal. They had experienced disease progression despite prior treatment or were intolerant of or unwilling to take sorafenib.

Looking at the escalation and expansion cohorts together, about 80% were men, half were white, 45% were Asian, and the median age was 63 years. A quarter had hepatitis B (and had to be on suppressive antiviral therapy), 23% had hepatitis C, and 51% were not infected with either virus; people with HBV/HCV coinfection were excluded.

The primary study endpoints were safety and tolerability in the escalation segment and objective response in the in the expansion segment. Secondary endpoints included time to response, duration of response, and overall survival. Preliminary results from the dose escalation cohort were previously presented at the 2015 American Society of Clinical Oncology annual meeting.

The most common treatment-related side effects were fatigue (18%), pruritus (15%), skin rash (14%), diarrhea (9%), and nausea (6%).

Objective responses to nivolumab monotherapy in patients with HCC "occurred early and were durable irrespective of infection status, were observed regardless of prior sorafenib treatment, and occurred in patients irrespective of PD-L1 expression on tumor cells," the researchers concluded.

"The overall survival rate was encouraging and notable disease stabilization was observed, including in some patients who progressed on prior sorafenib therapy," they added. "The manageable safety profile was similar to what has been observed in other tumor types without any new safety signals."

This study "challenges the assumption that immune therapy cannot be effective for patients with a high tumor burden," Sangro said.

A randomized Phase 3 study comparing nivolumab versus sorafenib for first-line treatment of people with advanced HCC is now enrolling (CheckMate 459/NCT02576509).